Treating cancer is clearly a very difficult process, and while progress has been made, much work remains to be done. The failures of many seemingly promising compounds to meet expectations have taught us that we must aggressively continue to develop new, innovative research methods to discover new anticancer agents. The objective of this Phase 1 SBIR project is to identify novel anticancer compounds existing at minor concentrations in unstudied plants, so that they can inspire the next generation of anticancer drugs. Sequoia Sciences is a recognized leader in natural products chemistry. Sequoia's published and unpublished data overwhelmingly suggest that new chemical diversity exists at minor concentrations in plants, and that some of these compounds are readily synthetically attainable. In this Phase 1 SBIR proposal, Sequoia presents compelling data on extensively purified and dereplicated chromatographic fractions that inhibit the growth of human tumor cell lines. These data suggest that compounds with novel chemical structures and novel inhibitory activities will be identified during this Phase 1 SBIR. In the era of combinatorial chemistry, genomics, and structure-aided drug design, it is tempting to think that the structural diversity evolved in nature is no longer needed;it has become resoundingly clear, however, that these new technologies alone will not meet the needs of the rapidly aging US population. Medicinal chemists immediately require new structural inspiration from the distinct chemical space occupied by natural products. This Phase 1 SBIR proposes a detailed plan to provide this new structural inspiration for medicinal chemists. PUBLIC HEALTH RELEVANCE: According to the NCI, 565,560 people will die from cancer in 2008 the United States alone. Based on rates from 2003-2005, it is likely that 43% of all people born today will be diagnosed with some form of cancer. Treating cancer is clearly a very difficult process, and while progress has been made, much work remains to be done. It has become resoundingly clear, however, that current technologies alone will not meet the needs of the rapidly aging US population. The objective of this Phase 1 SBIR project is to identify novel anticancer compounds existing at minor concentrations in unstudied plants, so that they can inspire the next generation of anticancer drugs. Medicinal chemists immediately require new structural inspiration from the distinct chemical space occupied by natural products.